The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease.
OBJECTIVE
To determine whether aspirin and antioxidant therapy, combined or alone, are more effective than placebo in reducing the development of cardiovascular events in patients with diabetes mellitus and asymptomatic peripheral arterial disease.


METHODS
Multicentre, randomised, double blind, 2x2 factorial, placebo controlled trial.


METHODS
16 hospital centres in Scotland, supported by 188 primary care groups.


METHODS
1276 adults aged 40 or more with type 1 or type 2 diabetes and an ankle brachial pressure index of 0.99 or less but no symptomatic cardiovascular disease.


METHODS
Daily, 100 mg aspirin tablet plus antioxidant capsule (n=320), aspirin tablet plus placebo capsule (n=318), placebo tablet plus antioxidant capsule (n=320), or placebo tablet plus placebo capsule (n=318).


METHODS
Two hierarchical composite primary end points of death from coronary heart disease or stroke, non-fatal myocardial infarction or stroke, or amputation above the ankle for critical limb ischaemia; and death from coronary heart disease or stroke.


RESULTS
No evidence was found of any interaction between aspirin and antioxidant. Overall, 116 of 638 primary events occurred in the aspirin groups compared with 117 of 638 in the no aspirin groups (18.2% v 18.3%): hazard ratio 0.98 (95% confidence interval 0.76 to 1.26). Forty three deaths from coronary heart disease or stroke occurred in the aspirin groups compared with 35 in the no aspirin groups (6.7% v 5.5%): 1.23 (0.79 to 1.93). Among the antioxidant groups 117 of 640 (18.3%) primary events occurred compared with 116 of 636 (18.2%) in the no antioxidant groups (1.03, 0.79 to 1.33). Forty two (6.6%) deaths from coronary heart disease or stroke occurred in the antioxidant groups compared with 36 (5.7%) in the no antioxidant groups (1.21, 0.78 to 1.89).


CONCLUSIONS
This trial does not provide evidence to support the use of aspirin or antioxidants in primary prevention of cardiovascular events and mortality in the population with diabetes studied.


BACKGROUND
Current Controlled Trials ISRCTN53295293.
Belch
Jill
J
Institute of Cardiovascular Research, University of Dundee, Ninewells Hospital, Dundee DD1 9SY. J.J.F.Belch@dundee.ac.uk
MacCuish
Angus
A
Campbell
Iain
I
Cobbe
Stuart
S
Taylor
Roy
R
Prescott
Robin
R
Lee
Robert
R
Bancroft
Jean
J
MacEwan
Shirley
S
Shepherd
James
J
Macfarlane
Peter
P
Morris
Andrew
A
Jung
Roland
R
Kelly
Christopher
C
Connacher
Alan
A
Peden
Norman
N
Jamieson
Andrew
A
Matthews
David
D
Leese
Graeme
G
McKnight
John
J
O'Brien
Iain
I
Semple
Colin
C
Petrie
John
J
Gordon
Derek
D
Pringle
Stuart
S
MacWalter
Ron
R
D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control*; D003925:Diabetic Angiopathies / Q000517:prevention & control*; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000517:prevention & control*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
D000975:Antioxidants; D010975:Platelet Aggregation Inhibitors; D001241:Aspirin